Benznidazole

Uses

Benznidazole is a trypanocidal agent used to treat Chagas disease.

For use in the treatment of Chagas disease in children 2-12 years of age .

Benznidazole is also used to associated treatment for these conditions: Chagas' Disease caused by Typanosoma cruzi

How Benznidazole works

Benznidazole is thought to be reduced to various electrophilic metabolites by nitroreductases present in Trypanosoma cruzi . These metabolites likely bind to proteins, lipids, DNA, and RNA resulting in damage to these macromolecules. Benznidazole has been found to increase trypanosomal death through interferon-γ which is likely present in increased amounts due to inflammation caused by macromolecule damage . DNA in parasites affected by benznidazole has been found to undergo extensive unpacking with overexpression of DNA repair proteins supporting the idea of DNA damage contributing to the mechanism of the drug .

Toxicity

At clinically relevant dosages, benznidazole can produce hepatotoxicity, peripheral neuropathy, and angioedema .

Food Interaction

• Take with or without food.

[Major] CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients.

There have been a few case reports involving metronidazole, although data overall are not convincing.

The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram.

Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'.

Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion.

Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.

However, some investigators have questioned the disulfiram-like properties of metronidazole.

One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction.

Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

Benznidazole Disease Interaction

Major: Cockayne syndromeModerate: bone marrow depression, liver dysfunction, renal dysfunction

Volume of Distribution

The apparent volume of distribution is 39.19 L .

Elimination Route

Benznidazole has a bioavailability of 91.7% and a Tmax of 2.93 h .

Half Life

The half life of elimination is 13.27 h .

Clearance

The apparent oral clearance is 2.04 L/h .

Elimination Route

The metabolites of benznidazole appear to be primarily exreted in the urine .

Innovators Monograph

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